CAREER: MOEMS-based Head-mounted NIR-II Microscopy for Molecular Imaging of Brain Tumor in Freely Behaving Small Animal Models

在美国，脑疾病是一个相当大的社会和经济负担。脑部疾病每年的成本约为8000亿美元，估计每年有5000万人受到影响，对科学家来说是一个巨大的挑战。目前，尽管许多研究者做出了努力，并投入了大量资金，但仍没有有效的治疗脑疾病（尤其是胶质母细胞瘤）的方法。为了帮助神经肿瘤学家研究脑肿瘤的基本机制和配体-受体相互作用的动力学，小型化的深部组织成像工具是一个迫切而未被满足的需求。该项目将重点开发一种微型显微镜，用于对行为自由的小动物进行分子靶向成像。这项研究的最终目标是提供先进的生物医学工具，以推动科学理解和未来临床应用的进步。这些技术可能会为临床医生带来新的成像引导手术和治疗方法，以改善相当数量人群的生活质量。广义分子成像策略将应用于其他器官，如乳腺、肺和结肠。将为密歇根州立大学和周边社区（大兰辛）开展跨学科教育活动，重点是增加妇女和代表性不足的少数民族的参与。本项目旨在开展头戴式近红外- ii共聚焦荧光显微镜的研究，该显微镜可对脑肿瘤进行深度（1000µm）的体内纵向细胞分辨率成像，用于研究与胶质母细胞瘤等脑病相关的肿瘤生物标志物的分子造影剂。光纤耦合超导纳米线单光子探测器实现了生物透明窗口（1000-1700nm）的深度成像。基于磁场兼容的超低功耗薄膜压电材料和基于全介电介质的平面透镜，将开发具有远距聚焦可调的浑浊脑瘤深部微系统三维激光扫描引擎。在一个微小的平台上集成单片焦点调谐和波束转向设备，可以实现超低功耗的宽带扫描，这在目前的宏观仪器中是不可能的。显微系统的发展将有助于开拓光电子学在单光子探测方面的新知识。深入了解生物标志物的多模态成像将为开发新的成像模式在基础癌症生物学研究和转化医学中的应用奠定基础。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Brain diseases represent a considerable social and economic burden in US. With yearly costs of about 800 billion and an estimated 50 million people afflicted per year, brain diseases are a grand challenge for scientists. Presently, there is no effective cure for brain diseases (especially glioblastoma) despite the efforts of many investigators and significant financial investment. There is a pressing and unmet need for miniaturized deep tissue imaging tools that can help neuro-oncologist study the fundamental mechanism of brain tumor and the dynamics in the ligand-receptor interactions. This project will be focused on the development of a tiny microscope for molecularly targeted imaging on freely behaving small animals. The ultimate goal of this research is to provide advanced biomedical tools to drive advancements in both scientific understanding and future clinical applications. The techniques may lead to new imaging-guided surgery and therapies for clinicians to improve the quality of life for a sizable population. The generalized molecular imaging strategies will be applied to other organs, such as the breast, lung, and colon. Interdisciplinary educational activities will be developed for MSU and surrounding communities (Greater Lansing) with emphasis on increasing participation by women and underrepresented minorities.This project aims to conduct research leading to head-mounted near-infrared-II confocal fluorescence microscope that allows in vivo longitudinal cellular resolution imaging of brain tumor with deep penetration (1000µm) for studying molecular contrast agents targeting tumor biomarkers associated with brain diseases, including glioblastoma. Fiber-coupled superconductive nanowire single photon detector enables deep imaging in the biological transparency window (1000-1700nm). Based on magnetic field-compatible ultra-low power thin-film piezoelectrical materials and all-dielectric metamaterials-based flat lens, micro-system enabled three-dimensional laser scan engine with long-range focus tunability deep in the turbid solid brain tumor will be developed. Integration of monolithic focus tuning and beam steering devices on a tiny platform allows broad-bandwidth scan with ultra-low power consumption, which is currently impossible with macro-scale instrumentation. The development of microscopic system will help exploit new knowledge of opto-electronics on single photon detection. In-depth understanding of multimodal imaging on biomarkers will lay the foundation for developing new imaging modalities for applications in basic cancer biology studies and translational medicine.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.